This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Amyloids are formed when proteins change conformation to form insoluble fibers that can cause severe damage and death. Amyloidoses include Alzheimer's disease and a variety of prion diseases including Creutzfeldt-Jakob and BSE ("mad cow disease"). Mammalian prions are formed by the protein PrP. Amyloid proteins share a cross-beta structure, but have resisted characterization by crystallography and NMR. Fiber diffraction, in combination with electron microscopy, offers the best hope for structure determination. Structural studies are needed to answer fundamental protein folding questions, to understand amyloid formation, and for rational drug design. We use dried fibers made under controlled conditions. Improved prion availability, improved methods of specimen preparation, and synchrotron radiation offer unprecedented opportunities to obtain improved amyloid diffraction data. We collected wide-angle data in August 2008, from a number of infectious prion samples, both brain-derived and recombinant. These data are proving to be invaluable in developing molecular models, showing experimentally for the first time that a four-stranded beta structure is the repeating unit, at least in some prion strains. We also collected data from a 7-residue fragment of the yeast prion protein Sup35, and from a long (55 residues) fragment of the mammalian prion protein. The prion data were the first diffraction data from infectious prions to be obtained at APS.